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The West of Scotland Cohort of Mitochondrial Individuals with the m.3243A>G Variant: Variations in Phenotypes and Predictors of Disease Severity

Lookup NU author(s): Professor Grainne Gorman



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


BACKGROUND: The m.3243A>G variant is the commonest mitochondrial (mt) DNA pathogenic variant and a frequent cause of mitochondrial disease. Individuals present with a variety of clinical manifestations from diabetes to neurological events resembling strokes. Due to this, patients are commonly cared for by a multidisciplinary team. OBJECTIVES: This project aimed to identify patients with confirmed mt.3243A>G-related mitochondrial disease attending the Muscle Clinic at Queen Elizabeth University Hospital in Glasgow. We explored potential correlates between clinical phenotypes and mtDNA heteroplasmy levels, HbA1c levels, body mass index, and specific clinical manifestations. We investigated if there were discrepancies between non-neurological speciality labelling in clinical records and individuals' phenotypes. METHODS: Data were gathered from the West of Scotland electronic records. Phenotypes were ascertained by a clinician with expertise in mitochondrial disorders. Statistical analyses were applied to study relationships between tissue heteroplasmy, HbA1c and clinical phenotypes including body mass index (BMI). RESULTS: Forty-six individuals were identified from 31 unrelated pedigrees. Maternally inherited diabetes and deafness was the prominent syndromic phenotype (48%). A significant association was found between overall number of symptoms and bowel dysmotility (p < 0.01). HbA1c was investigated as a predictor of severity with potential association seen. Although used widely as a prognosticator, neither corrected blood nor urine mtDNA heteroplasmy levels were associated with increased number of symptoms. In 74.1% of records, syndromic phenotypes were incorrectly used by non-neurological specialities. CONCLUSIONS: This m.3243 A > G patient cohort present with marked clinical heterogeneity. Urine and blood heteroplasmy levels are not reliable predictors of disease severity. HbA1c may be a novel predictor of disease severity with further research required to investigate this association. We infer that prognosis may be worse in patients with low BMIs and in those with bowel dysmotility. These results underscore a multidisciplinary approach and highlight a problem with inaccurate use of the existing nomenclature.

Publication metadata

Author(s): Saunders C, Longman C, Gorman G, James K, Oliwa A, Petty R, Snadden L, Farrugia ME

Publication type: Article

Publication status: Published

Journal: Journal of Neuromuscular Diseases

Year: 2024

Volume: 11

Issue: 1

Pages: 179-189

Online publication date: 02/01/2024

Acceptance date: 12/12/2023

Date deposited: 12/02/2024

ISSN (print): 2214-3599

ISSN (electronic): 2214-3602

Publisher: IOS Press


DOI: 10.3233/JND-230166

PubMed id: 38108361


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